The present invention relates generally to a method for treating glaucoma, and more particularly to such a method which uses chronic oral administration of ethacrynic acid or an analog thereof in order to safely and effectively lower intraocular pressure in the human eye.
Glaucoma is a condition of the eye characterized by elevated intraocular pressure (for adults, any pressure above about 21 mm Hg). It is a chronic, blinding disease affecting millions worldwide, and is currently treated with a number of medications with varying degrees of safety and efficacy. Thus, since this is such a serious condition, researchers are continually attempting to develop treatments which could relieve or possibly cure the condition.
In 1968, Drs. Peczon and Grant explored the use of diuretic drugs for treating glaucoma with the aim of determining whether they affect the formation of aqueous humor. The drugs tested, in acute dosages, were ethacrynic acid, chlormerodrin, bendroflumethiazide, furosemide, and triamterene, these drugs being five chemically and pharmacologically different types. The tests were compared to tests of acetazolamide, a carbonic anhydrase inhibitor having a known effect on intraocular pressure in glaucomatous patients when administered acutely. The conclusions drawn from the tests indicated that, in patients with open angle glaucoma, no consistent reduction of ocular pressure was induced by ethacrynic acid, chlormerodrin, bendroflumethiazide or triamterene administered orally, and only slight reduction by furosemide, distinctly less than by acetazolamide. In conclusion, the report stated that none of various categories of diuretic agents had yet been found to the interfere with aqueous formation or to reduce ocular pressure as effectively as the carbonic anhydrase inhibitors and the hypertonic osmotic agents.
In U.S. Pat. No. 4,757,089 issued to Epstein, a method of increasing aqueous humor outflow is disclosed. The method comprises topically administering to the eye a compound containing one or more groups capable of reacting with sulfhydryl groups in the trabecular meshwork of the eye. A further embodiment comprises the microinjection of such a compound into the trabecular meshwork. The preferred compound is ethacrynic acid. Although the invention appears to provide effective, non-surgical treatment of glaucoma, the topical administration of ethacrynic acid to the eye may produce medically unacceptable side effects.
Topical ethacrynic acid mixed with cysteine drops has also been tested. The results showed a lowering in intraocular pressure in rabbits and cynomolgus monkeys when combined with n-acetyl cysteine pre-treatment to reduce corneal toxicity.
Thus, it is an object of the present invention to provide a method for treating glaucoma which is non-surgical, will safely and effectively lower the intraocular pressure of the eye without use of a masking agent, without medically unacceptable side effects, and can be self-administered by the patient under periodic medical supervision. It is a further object of the present invention to advantageously provide such a method which may also have a long term effect on lowering intraocular pressure. It is yet a further object of the present invention to provide such a method which may also be additive in effect, or enhance the effect of intraocular pressure lowering when administered with other agents.